The focus of this project is the use of magnetic resonance imaging to understand the pathophysiology of multiple sclerosis (MS) and to determine whether disease activity is altered by various immunomodulatory treatments such as Insulin-like growth factors (rhIGF-1), and altered peptide ligand (APL) and to monitor the natural history of MS. Magnetization transfer (MT) imaging which is sensitive to the amount of bound and free water in the white matter and indirectly reflects myelination was also used to evaluate these patients. MT region of interest (ROI) analysis of individual enhancing or non-enhancing lesions reveals that there is no difference in the pattern of MS lesion recovery either when a lesion develops during the natural history of the disease or receiving INFB-1b. However, there does appear to be a faster improvement in the MTR recovery towards baseline when enhancing lesions occur in association with a clinical exacerbation requiring treatment with intravenous steroids. These results would indicate that closure of the blood brain barrier with steroids is associated with a decrease in the ratio of free to bound water within a MS lesion that is detected as a change in MTR. MTR studies performed of MS lesions in patients receiving rhIGF-1 suggest that a similar recovery pattern as observed with steroids which would be consistent with the proposed anti-inflammatory effects of this agent.The rhIGF-1 study closed in 1999 after enrollment of a total of seven MS patients, who completed the open-labeled baseline trial design with contrast enhancing lesions as primary outcome measure. The results of this study indicated that rhIGF-1 was safe and well tolerated in all patients and that further analysis of the primary and secondary outcome measures are still ongoing to determine therapeutic efficacy. A second open-labeled baseline versus treatment trial is evaluating Altered Peptide Ligand (APL) as a treatment for relapsing-remitting MS patients. APL is thought to interfere with binding of T-cells to antigen presenting cells and induce tolerance in MS patients. This trial was put on hold after three of seven patients developed clinical adverse effects of APL that were correlated to findings on MRI examination. Further immunologic-imaging evaluations of the patients following the cessation of APL therapy are underway in order to develop a better understanding of the mechanism of action of this approach to treating MS.